The principal objectives of this research proposal are to determine the relative incidence and significance of mechanical and hypoxic brain damage in adults and children with severe head injuries and in a model of acceleration head injury in the rhesus monkey, using as criteria the neurological examination; the measurements of intracranial pressure, cerebral blood flow, and metabolism; averaged evoked potentials; and neuropathology. Since we believe that hypoxic and ischemic hypoxia are common complications of head injury, we also propose to study in animals the sequence of events that leads to hypoxic brain damage at critical levels of cerebral perfusion pressure and systemic oxygenation, based on two hypotheses: 1) brain damage is not dependent on a failure of high energy phosphate metabolism; and 2) the weak link in persistent or irreversible hypoxic damage of the cell is failure of restoration of ion balance across the cell membrane. Edema is a common complication of brain contusions and lacerations and intracranial hematomas. We believe that edema per se may not interfere with brain function; but if it does so, the mechanism probably is a critical reduction in blood flow through the edematous tissue. Therefore, we propose to study the effects of edema on neurophysiological function and cerebral circulatory dynamics.